A drug delivery system (DDS) is a technique for effectively and locally delivering a drug to a targeted affected area (organ, tissue, cells, pathogen, or the like). Macromolecules and fine particles easily flow out of the blood vessel in tumor tissue because blood vessel permeability is significantly enhanced compared to in normal tissue. Substances reaching tumor tissue accumulate because the lymphoid system is not developed. Such a characteristic is called an EPR effect and is an important factor in passive targeting to cancer cells. However, although the EPR effect has enabled the cancer tissue-selective delivery/accumulation of a drug carrier administered into the blood vessel, it remains to be a challenge to sustainedly release the agent contained in the carrier effectively.
Meanwhile, attention has been given in recent years to hyperthermia chemotherapy and photodynamic therapy utilizing the heat-generating effect and the active oxygen-producing effect (PDT effect) of a dye having an absorption wavelength in the infrared region. These therapies utilize the transmission properties of near infrared light in the living body and a compound capable of absorbing near infrared light; for example, Patent Document 1 (JP 2010-69001 A) discloses photodynamic hyperthermia chemotherapy using indocyanine green (ICG) as a photosensitive dye agent to utilize its heat-generating and active oxygen-producing effects. This document describes that the injection of cisplatin and ICG into the site of tumor tissue of an animal followed by light irradiation resulted in no identification of the recurrence and metastasis of the tumor even after a lapse of 1 year after treatment.
Patent Document 2 (WO 00/41726) also discloses transdermal photodynamic therapy using a photosensitizer such as ICG. According to the invention of this document, a photosensitizing agent delivery system includes a liposome delivery system comprising a photosensitizing agent. The liposome delivery system adopts a form in which the photosensitizing agent is administered in the form of a liposome formulation (i.e., uses the photosensitizing agent by including it in a liposome). However, this document only describes the use of the photosensitizing agent in tumor tissue and does not disclose aspects such as the co-administration of an anti-cancer agent.
Patent Document 3 (JP 2007-277218 A) discloses a liposome composition comprising a hydrophilic drug included in the hydrophilic layer of the liposome and a hydrophobic photosensitive substance included in the lipid bilayer of the liposome, wherein the liposome is induced to release the hydrophilic drug by a photodynamic effect under irradiation by a light source. However, disclosed as the photosensitive substance is only porphyrin, and porphyrin has side effects including hypersensitivity such as solar dermatitis (pruritic rash, erythema, or blister); digestive symptoms such as nausea, gastrointestinal problems, diarrhea, stomach ache, and abdominal discomfort; and other side effects such as pigmentation, cardiac palpitation, feeling of heat, physical discomfort, hot flush, and black stool.
Patent Document 4 (JP 2010-266295 A) discloses a fluorescent tissue marker having a vesicle cluster obtained by including vesicles formed by the combination of a phospholipid and a near-infrared fluorescent dye such as indocyanine green in a hydrophilic solvent and forming and aggregating a plurality of capsules using an emulsifier. However, it is intended to be used as a fluorescent tissue marker, and the application thereof to photodynamic hyperthermia chemotherapy or the inclusion of an agent in a liposome is not contemplated.